by Jeffrey Laurence, M.D.

Published Wednesday, October 10, 2012

Through
numerous cycles of grants and awards, as well as targeted, collaborative
projects such as the ARCHE consortium, amfAR for many years has focused on research
towards a cure for AIDS. As noted in previous updates, people with HIV who are successfully
treated with antiretroviral drugs (ARVs) still have infected cells in which HIV
remains silent, invulnerable to attack by the immune system or standard
anti-HIV drugs, presenting a critical barrier to curing AIDS.

Dr. Keith JeromeUnique strategies
to destroy these viral reservoirs, through gene therapy, “shock and kill”
approaches (awakening virus, then killing it with ARVs), and enhanced immune
attack, are active areas of research. In the October issue of the Journal of Virology, Dr. Keith Jerome, a former amfAR grantee, discusses discusses a novel aspect of this work. Could strategies based on AIDS cure research—including the cure of the “Berlin patient” through a stem cell transplant—be used to cure other viral diseases that have similar latent reservoirs?

Working at
the University of Washington, Seattle, Dr. Jerome and colleagues suggest that
one might be able to target cells latently infected with hepatitis B virus
(HBV) or herpes simplex virus (HSV) using proteins known as nucleases. One of these
proteins can home in on specific DNA sequences of a virus and others can then cut
them out.

Like HIV, HBV
is of enormous public health importance. Despite having an effective vaccine, more
than 350 million people are chronically infected with HBV—about 10 times the
number chronically infected with HIV worldwide. In addition, HIV and HBV are
transmitted by the same risk factors and large numbers of people are co-infected
with both viruses. As these people age, the liver damage linked to HBV can
become more injurious than HIV itself. Similarly, genital HSV/HIV co-infection
is common, as HSV is a key risk factor for HIV acquisition and transmission,
and an HSV vaccine does not exist. But just like HIV, existing drug treatments
for HBV and HSV do not target latent viral stores.

Dr. Jerome
discusses how genetic information coding for three types of DNA cleaving
proteins—the zinc finger and the TAL (transcription activator-like) effector, as
well as homing endo-nucleases—could be incorporated into harmless viruses that
would target specific cells in the body infected with HIV, HBV, or HSV, and cut
them out. He suggests that nanotechnology approaches might enable delivery of
these proteins into hard-to-access places within the body, including the brain.

With further
refinement of this technology, Dr. Jerome and associates believe that “the
possibility of a viral cure exists.”
This is especially groundbreaking given that, to date, the only virus
for which there is evidence that a true cure has been found is hepatitis C.
Long a leader in funding trailblazing studies, amfAR proudly supports this
research.